Vanadium compounds have arisen as potential therapeutic agent for the treatment of cancers over the past decades. A few studies suggested that vanadyl complexes may discriminate between the cancerous and the normal cells. Here, we reported the investigation on the pro-apoptotic effect and the underlying mechanism of bis(acetylacetonato) oxovanadium(IV) ([VO(acac)₂]) on SH-SY5Y neuroblastoma cells in comparison with that of mouse primary cortex neurons. The experimental results revealed that [VO(acac)₂] showed about 10-fold higher cytotoxicity (IC50 ~16 μM) on the neuroblastoma cells than on normal neurons (IC50 ~250 μM). Further analysis indicated that the vanadyl complex suppressed the growth of neuroblastoma cells via different pathways depending on its concentration. It induced a special cyclin D-mediated and p53-independent cell apoptosis at <50 μM but cell cycle arrests at >50 μM. In contrast, [VO(acac)₂] promoted cell viability of primary neurons in the concentration range of 0–150 μM; while [VO(acac)₂] at hundreds of μM would cause neuronal death possibly via the reactive oxygen species (ROS)-mediated signal pathways. The extraordinary discrimination between neuroblastoma cells and primary neurons suggests potential application of vanadyl complexes for therapeutic treatment of neuroblastoma. In addition, the p53-independent apoptotic pathways induced by vanadyl complexes may provide new insights for future discovery of new anticancer drugs overcoming the chemo-resistance due to p53 mutation.

在过去的几十年中，钒化合物已经成为治疗癌症的潜在治疗剂。一些研究表明，钒基复合物可以区分癌细胞和正常细胞。在这里，我们报道了与小鼠原代皮层神经元相比，双（乙酰丙酮基）氧钒（IV）（[VO（acac）₂ ]）对SH-SY5Y神经母细胞瘤细胞的促凋亡作用及其潜在机制的研究。实验结果表明，[VO（acac）₂]显示出对神经母细胞瘤细胞的细胞毒性（IC50〜16μM）比对正常神经元（IC50〜250μM）高约10倍。进一步的分析表明，钒基复合物根据其浓度通过不同途径抑制神经母细胞瘤细胞的生长。它在<50μM时诱导了特殊的细胞周期蛋白D介导且不依赖p53的细胞凋亡，但在> 50μM时细胞周期停滞。相反，[VO（acac）₂ ]可以在0-150μM的浓度范围内促进原代神经元的细胞活力。而[VO（acac）₂]浓度为数百μM时，可能会通过活性氧（ROS）介导的信号通路导致神经元死亡。神经母细胞瘤细胞和原代神经元之间的非同寻常的区别表明，钒基复合物在神经母细胞瘤的治疗中具有潜在的应用前景。此外，钒基复合物诱导的非p53凋亡途径可能为将来发现克服因p53突变而引起的化学耐药性的新抗癌药物提供新的见解。